Diabetes Drug, Metformin, May Promote Longevity

Metformin, a common type 2 diabetes drug, shows promise in protecting against aging-related diseases, according to a new study.

Mounting evidence suggests metformin’s benefits beyond treating diabetes. Some studies indicate that the drug may play a role in preventing some aging-related illnesses, including cancer and Alzheimer’s disease. However, clinical trials of metformin in longevity are still in the early stages.

A research team from the School of Public Health, LKS Faculty of Medicine of the University of Hong Kong (HKUMed) assessed the target-specific effect of metformin on biomarkers of aging. The findings were published in The Lancet Healthy Longevity.

The researchers used data from 344,182 people from the U.K. Biobank, a large database that contains the genetic and health information of half of million individuals.

They examined four targets of metformin – AMP-activated protein kinase (AMPK), electron transfer flavoprotein dehydrogenase (ETFDH), glycerol-3-phosphate dehydrogenase 1 (GPD1), and presenilin enhancer 2 (PEN2).

Researchers looked at how these targets impact common biomarkers of aging, such as phenotypic age and leukocyte telomere length (LTL). The greater telomere length is thought to provide anti-aging benefits; however, the evidence is conflicting.

The research team found that glycated hemoglobin (HbA1c) lowering induced by the metformin target GPD1 was associated with younger phenotypic age and longer LTL, whereas AMPKγ2 was associated with younger phenotypic age only. They say this may partly be due to the glycaemic property of metformin.

"Increasing evidence suggests metformin may also exert its effect via glycaemic-independent pathways. Better understanding of mechanisms of metformin action using big data approaches and different omics is warranted and improves evaluation of its repositioning potential," Luo Shan, Research Assistant Professor, School of Public Health, HKUMed, says in a statement.

The study authors note they could not determine the overall effect of metformin because the contribution of metformin in healthy aging via different mechanisms is not well studied.

The U.S. Food and Drug Administration (FDA) approved metformin in 1994 to treat type 2 diabetes. It is also the only antidiabetic recommended by the American Diabetes Association (ADA) for pre-diabetes. The drug has a good safety profile and has long been on the World Health Organization’s (WHO) Model Lists of Essential Medicines.

The drug reduces blood glucose levels by decreasing glucose production in the liver, reducing intestinal absorption, and increasing insulin sensitivity.

Metformin also has several non-FDA-approved uses, such as gestational diabetes, management of weight gain caused by antipsychotics, type 2 diabetes prevention, and the treatment and prevention of polycystic ovary syndrome (PCOS).

This study provides genetic validation evidence that metformin and longevity might be linked. However, further research is needed.